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      RhoA/rho-kinase, nitric oxide and inflammatory response in LIMA during OPCABG with isoflurane preconditioning

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          Abstract

          Background

          Grafting vessel with LIMA to the left anterior descending coronary artery plays a most important role in the long-term prognosis of OPCABG surgery. The aim of this study was to compare the effects of isoflurane preconditioning on miRs and mRNAs levels in the left internal mammary arterie (LIMA) graft with propofol in patients undergoing off-pump coronary artery bypass surgery (OPCABG).

          Methods

          Patients were randomly assigned to receive either propofol ( n = 15), or interrupted isoflurane ( n = 15). In group P, propofol administration was continued at 3–5 mg/kg/h intravenous injection for the duration of surgery. Five minutes prior to incision, patients of the isoflurane group (group Iso) received 2 cycles of 1 MAC isoflurane.

          Results

          miR-221 were significantly lower in group Iso ( P < 0 .05). E-selectin mRNA, RhoA mRNA and ROK mRNA were significantly lower at specimens of LIMA in group Iso compared with those in group P patients ( P < 0 .05). The expression of NOS3 mRNA was significantly higher in group Iso patients ( P < 0 .05).

          Conclusion

          Our findings provide some insight that prior interrupted isoflurane administration could regulate miR-221, and downstream effectors (mRNAs) and resulted in actual attenuation of inflammation and spasm of LIMA in patients undergoing OPCABG surgery.

          Trial registration

          NCT No. ( ClinicalTrials.gov): NCT02678650; Registration date: January 23, 2016.

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          Most cited references28

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          Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells.

          Dicer is a key enzyme involved in the maturation of microRNAS (miRNAs). miRNAs have been shown to be regulators of gene expression participating in the control of a wide range of physiological pathways. To assess the role of Dicer and consequently the importance of miRNAs in the biology and functions of human endothelial cells (EC) during angiogenesis, we globally reduced miRNAs in ECs by specific silencing Dicer using siRNA and examined the effects on EC phenotypes in vitro. The knockdown of Dicer in ECs altered the expression (mRNA and/or protein) of several key regulators of endothelial biology and angiogenesis, such as TEK/Tie-2, KDR/VEGFR2, Tie-1, endothelial nitric oxide synthase and IL-8. Although, Dicer knockdown increased activation of the endothelial nitric oxide synthase pathway it reduced proliferation and cord formation of EC in vitro. The miRNA expression profile of EC revealed 25 highly expressed miRNAs in human EC and using miRNA mimicry, miR-222/221 regulates endothelial nitric oxide synthase protein levels after Dicer silencing. Collectively, these results indicate that maintenance and regulation of endogenous miRNA levels via Dicer mediated processing is critical for EC gene expression and functions in vitro.
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            MicroRNAs and Endothelial (Dys) Function.

            Accumulating evidence indicates that microRNAs (miRs)-non-coding RNAs that can regulate gene expression via translational repression and/or post-transcriptional degradation-are becoming one of the most fascinating areas of physiology, given their fundamental roles in countless pathophysiological processes. The relative roles of different miRs in vascular biology as direct or indirect post-transcriptional regulators of fundamental genes implied in vascular remodeling designate miRs as potential biomarkers and/or promising drug targets. The mechanistic importance of miRs in modulating endothelial cell (EC) function in physiology and in disease is addressed here. Drawbacks of currently available therapeutic options are also discussed, pointing at the challenges and clinical opportunities provided by miR-based treatments. J. Cell. Physiol. 231: 1638-1644, 2016. © 2015 Wiley Periodicals, Inc.
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              Hydrogen sulfide and nitric oxide interactions in inflammation.

              Together with carbon monoxide (CO), nitric oxide (NO) and hydrogen sulfide (H2S) form a group of physiologically important gaseous transmitters, sometimes referred to as the "gaseous triumvirate". The three molecules share a wide range of physical and physiological properties: they are small gaseous molecules, able to freely penetrate cellular membranes; they are all produced endogenously in the body and they seem to exert similar biological functions. In the cardiovascular system, for example, they are all vasodilators, promote angiogenesis and protect tissues against damage (e.g. ischemia-reperfusion injury). In addition, they have complex roles in inflammation, with both pro- and anti-inflammatory effects reported. Researchers have focused their efforts in understanding and describing the roles of each of these molecules in different physiological systems, and in the past years attention has also been given to the gases interaction or "cross-talk". This review will focus on the role of NO and H2S in inflammation and will give an overview of the evidence collected so far suggesting the importance of their cross-talk in inflammatory processes. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                zhangliangyoyo27@sina.com
                chengbinwang_mz@126.com
                boli_xinwai@163.com
                duomaolin_mz@163.com
                junma_mazui@163.com
                Journal
                J Cardiothorac Surg
                J Cardiothorac Surg
                Journal of Cardiothoracic Surgery
                BioMed Central (London )
                1749-8090
                25 January 2019
                25 January 2019
                2019
                : 14
                : 22
                Affiliations
                [1 ]ISNI 0000 0004 1761 5917, GRID grid.411606.4, Department of Anesthesiology, , Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, ; No.2 Anzhen Road, Chaoyang District, Beijing, 100029 China
                [2 ]ISNI 0000 0004 1761 5917, GRID grid.411606.4, Department of Cardiac Surgery, , Beijing Anzhen Hospital, Capital Medical University-Beijing Institute of Heart Lung and Blood Vessel Diseases, ; No.2 Anzhen Road, Chaoyang District, Beijing, 100029 China
                Article
                835
                10.1186/s13019-019-0835-9
                6347768
                30683137
                e67219a2-3d86-4e5a-8e57-ee5193fcf916
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 April 2018
                : 14 January 2019
                Funding
                Funded by: National Nature Science Foundation of China
                Award ID: 81471902
                Award Recipient :
                Funded by: Beijing Health System High-Level Health Technical Talents Cultivation Fund
                Award ID: 2013-2-004
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Surgery
                isoflurane,left internal mammary artery,opcabg
                Surgery
                isoflurane, left internal mammary artery, opcabg

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